The increase in alcohol (ALC) use and abuse by adolescents during recent years poses several risks for them associated with growth, endocrine functions and development. The overall goal of this study is to obtain information which will allow us to better understand the detrimental effects and mechanisms of action of ALC on the female pubertal process. The studies proposed will assess influences of specific puberty related peptides, the involvement and activation of important genes critical to brain events leading to mammalian puberty, and discern the effects of ALC on their actions and interactions. In vivo and in vitro techniques using molecular and physiological approaches will be utilized following chronic and acute ALC exposure to address six aims which will collectively allow us to determine what factors are involved, the mechanisms of interference and potential means to reverse the detrimental effects of ALC on puberty related events. Aim 1 will assess the effects of ALC on the synthesis of specific puberty related hypothalamic genes and proteins, with the results being correlated with hypothalamic, pituitary and ovarian hormones, as well as other indices of puberty. Aim 2 will assess regulation of hypothalamic genes by peptides involved at puberty and determine the actions of ALC. Aim 3 will assess the expression and regulation of glial and neuronal signaling-adhesion genes at puberty and determine the effects of ALC. Aim 4 will assess the effects of ALC on the hypothalamic action of specific peptides that induce luteinizing hormone releasing hormone (LHRH) secretion at puberty. Aim 5 will use cultured rat hypothalamic astrocytes and an LHRH neuronal cell line to further assess glial-neuronal mechanisms associated with LHRH secretion, determine the actions of ALC, and investigate potential means for reversal of ALC actions. Aim 6 will test the ability of specific substances in vivo to protect against or reverse ALC-induced delayed puberty. This research, which is relevant to adolescent health and development, is intended to further identify consequences of ALC consumption with regard to hormonal events and their actions which can alter female pubertal maturation. Narrative The information gained from this study will allow us to better understand the detrimental effects and mechanisms of action of alcohol (ALC) on the female pubertal process. The studies proposed will assess influences of specific puberty related peptides, the involvement and activation of important genes critical to brain events leading to mammalian puberty, and discern the effects of ALC on their actions and interactions. This research, which is relevant to adolescent health and development, is intended to further identify consequences of ALC consumption with regard to hormonal events and their actions which can alter female pubertal maturation.